This application proposes renewal of the UNC Breast Cancer SPORE. Originally funded in 1992, the UNC SPORE has used significant institutional investment and the distinctive SPORE elements: funding flexibility, interdisciplinary collaboration, bidirectional translational research, developmental programs, and interSPORE partners to build an outstanding program in translational breast cancer research. The UNC SPORE's combination of population-based research, molecular genetics, breast cancer biology, health disparities research, tissue-acquiring clinical trials, database development, and expertise in bioinformatics and biostatistics was made possible with long-term SPORE support. Interaction between disciplines has resulted in substantial productivity, as measured by important findings published in excellent journals, career advancement for junior investigators, developmental research leading to grants and new SPORE projects, multiple funded interSPORE collaborations, and innovative approaches to breast cancer etiology, classification, prognosis, and therapy. Our five projects are conceptually linked by studies of breast cancer molecular phenotypes, particularly those with the worst prognosis: basal-like tumors, luminal B tumors, and tumors that overexpress HER2. Led by basic and clinical science teams, these projects feature our continuing population science study, the Carolina Breast Cancer Study, and three translational clinical trials. Data from multiple national and international trials will also be incorporated into our analyses. The projects are entitled: 1) Carolina Breast Cancer Study: Genetic susceptibility for breast cancer subtypes in African Americans and whites 2) Breast cancer vaccine strategies for HER2 and luminal B tumors 3) Determination of breast cancer subtype sensitivities to standard chemotherapy and combination chemotherapy-biologic regimens 4) Molecular portraits of human breast cancer endothelium 5) HER4 Isoforms: Tumor suppressor action and prognostic significance They are supported by strong infrastructure and institutional commitment from the University of North Carolina, its UNC Lineberger Comprehensive Cancer Center, and its Schools of Medicine and Public Health. SPORE investigators will have access to Cancer Center core facilities as well as SPORE funded cores. Specific to the SPORE are Genomics, Genotyping &Bioinformatics, Tissue Procurement &Analysis, Biostatistics, and Administration.